Single-nucleotide polymorphisms in the promoter region influence the expression of the human follicle-stimulating hormone receptor

Objective: To characterize novel single-nucleotide polymorphisms (SNPs) in human FSH receptor (FSHR) promoter region. Design: Retrospective and basic research study. Setting: University hospital. Patients: Women (202 from Germany and 55 from Indonesia) with male or tubal factor infertility undergoing controlled ovarian stimulation for IVF treatment. Interventions: None. Main Outcome Measure(s): Frequency, distribution, and correlation with clinical data of the SNPs. Dual luciferase assays and electrophoretic mobility shift assays (EMSA) Result(s): We identified two SNPs and three mutations in the promoter region of the human FSHR which could be allocated to positions -29, -37, -114, -123, and -138 upstream of the translation initiation codon. One SNP showed a high incidence (-29; 44%, n = 202), but no correlation with basal FSH serum levels or ovarian response with the SNP at position -29 was found. Luciferase reporter assays, using pGL3 vector constructs, showed that mutations at positions -37 and -138 lead to significantly higher promoter activity. EMSA indicate that putative binding sites for transcription factors are affected by the SNPs. Conclusions: The newly identified SNPs do not seem to influence clinical parameters substantially, but modulate expression of the FSHR via changes in transcription factor binding sites.